In blood, lipids are always present as lipoproteins. The mechanisms of transport and metabolism of lipids by the mediation of lipoproteins are now being clarified.
Triglycerides (TGs), cholesterols, and cholesteryl esters (CEs) are secreted in the form of very low density lipoproteins (VLDLs) into blood. VLDLs act to provide peripheral tissue with a portion of TGs in the form of fatty acids, and also participate in transfer and exchange of a portion of lipids between HDLs and intermediate lipoproteins (IDLs). IDLs, which undergo lipid exchange with HDLs, lose TGs, to thereby become low density lipoproteins (LDLs), which in turn are taken into peripheral tissue and supply cholesterols.
Meanwhile, cholesterols which have become useless in the peripheral tissue are withdrawn by HDLs and converted into CEs, and subsequently exchanged with TG contained in the above-mentioned TG-rich VLDLs, IDLs, or LDLs, until they are reversely transported to the liver. This process of transferring cholesterols from the peripheral tissue such as blood walls to the liver is known as reverse cholesterol transport (RCT), and this process is considered to contribute to prevention of excessive build-up of cholesterols (Medical Practice, vol. 18, No. 3, 473-480 (2001)).
Substances that are known to play an important role in the reverse cholesterol transport or lipid exchange between HDLs and TG-rich lipoproteins include enzymes such as lecithin cholesteryl acyltransferase (LCAT), hepatic lipase (HTLC), lipoprotein lipase (LPL), and cholesteryl ester transport proteins (CETP). However, their action mechanisms, interactions between lipoproteins, and relation with lipid metabolic errors have not yet been elucidated.
Foam cells take part in cholesterol build-up in the peripheral tissue. That is, macrophages derived from monocytes in blood and present in the walls of blood vessels gobble up fat and accumulate large amounts of fat particles (primarily CEs) therein. Chemically modified LDLs are taken into the macrophage cells endlessly by the mediation of scavenger receptors, whereby foam cells are formed. Emerging of foam cells is known to be a factor critical to the onset and development of arteriosclerosis in high cholestrolemia.
An object of the present invention is to provide novel information useful for elucidating interactions between HDL and TG-rich lipoproteins.
The present invention also provides information about a specific component of TG-rich lipoproteins which participate in the above interactions, regions of such component, and structures, and further provides an HDL-reactive peptide having a specific structure.
The present invention also provides novel information about interactions between cholesterols built up in peripheral tissue such as blood vessel walls and lipoproteins, and in particular information concerning cholesterol efflux mechanism.
Moreover, the present invention provides means useful for the evaluation and amelioration of lipid metabolic errors which greatly affect the onset, development, prognosis, etc. of heart diseases such as myocardial infarction as well as different types of arteriosclerosis, including cerebrovascular disorders such as cerebral apoplexy.